Contractile activity of smooth muscle in the arterial wall is responsible for regulating blood flow to all vital organs, including heart and brain. There exist chronic and/or pathophysiological conditions in which the vasculature fails to maintain the proper flow of oxygen and nutrients to body tissues; for example, hemorrhagic shock, chronic hypertension, coronary artery spasm and cerebral vasospasm. In all muscle types, it is known that intracellular Ca ion is the key regulatory substance in activating contraction. While in striated muscles, activator Ca ion binds directly to the contractile protein complex, work of the past several years indicates that internal Ca ion activates vertebrate smooth muscles indirectly by activating an associated enzyme system which phophorylates a regulatory subunit of myosin. Recent work with intact arteries however strongly suggests that additional regulatory steps are likely involved. We propose a model of the actomyosin cross-bridge cycle in smooth muscle which serves such a regulatory role and experiments to critically test the model. In preliminary experiments, we have found conditions under which vascular smooth muscle becomes contracted in the complete absence of Ca ions, by upsetting the normal balance between concomitant phosphorylation and dephosphorylation of the myosin regulatory light chains. A similar defect in situ would lead to a chronic vascular contraction not readily susceptible to normal means of vasodilation. We propose experiments to determine if such a mechanism in fact plays a role in disorders of the above type.